Martin Feuchtenberger

Publications of Martin Feuchtenberger

• Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study.

  Authors: Stefan Kleinert, Hans-Peter Tony, Andreas Krause, Martin Feuchtenberger, Siegfried Wassenberg, Constanze Richter, Ekkehard Röther, Wolfgang Spieler, Holger Gnann, Bianca M Wittig

  Rheumatology international. 08/2011;

  The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and toThe objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9-3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.

• Expression of K2P5.1 potassium channels on CD4+ T lymphocytes correlates with disease activity in rheumatoid arthritis patients.

  Authors: Stefan Bittner, Nicole Bobak, Martin Feuchtenberger, Alexander M Herrmann, Kerstin Göbel, Raimund W Kinne, Anker J Hansen, Thomas Budde, Christoph Kleinschnitz, Oliver Frey, Hans-Peter Tony, Heinz Wiendl, Sven G Meuth

  Arthritis research & therapy. 02/2011; 13(1):R21.

  CD4+ T cells express K(2P)5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cellCD4+ T cells express K(2P)5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K(2P)5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K(2P)5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Expression levels of K(2P)5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K(2P)5.1. K(2P)5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K(2P)5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K(2P)5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Disease activity in RA patients correlates strongly with K(2P)5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K(2P)5.1 as a potential biomarker for disease activity and differential diagnosis.

• Vaccination survey in patients with rheumatoid arthritis: a cross-sectional study.

  Authors: Martin Feuchtenberger, Stefan Kleinert, Sven Schwab, Petra Roll, Eva Christina Scharbatke, Eva Ostermeier, Reinhard E Voll, Arne Schäfer, Hans-Peter Tony

  Rheumatology international. 02/2011;

  The objective of this study is to evaluate the vaccination status in rheumatoid arthritis (RA) patients during routine clinical practice, data from a German non-interventional cross-sectional study.The objective of this study is to evaluate the vaccination status in rheumatoid arthritis (RA) patients during routine clinical practice, data from a German non-interventional cross-sectional study. In this prospective study, patients with rheumatoid arthritis were interviewed using a standardized questionnaire focusing on vaccination. Available vaccination documents were evaluated, and titers for common vaccination antigens (hepatitis B, rubella, mumps, measles, diphtheria, tetanus) were analyzed with special regard to the underlying treatment and age of patients. A total of 301 RA patients treated with conventional DMARDs alone (cohort I, n = 125), TNF-blocking agents (cohort II, n = 117), or B-cell depletion with rituximab (cohort III, n = 59) have been studied. Significantly more patients in the biologic cohorts II and III were aware of an increased risk of infections (I: 67.7%, II: 83.8%*, III: 89.9%*, P < 0.05). Pneumococcal vaccination rate was significantly higher (I: 20.2%, II 36.8%* and III: 39.0%*, P < 0.05) compared with cohort I. Differences were less evident for influenza. Significantly more patients ≥60 years of age have been vaccinated against Streptococcus pneumoniae and influenza. An obvious discrepancy existed between vaccination awareness and actual vaccination rates for all cohorts. No significant differences in vaccination titers could be seen between the three cohorts. Awareness of infectious complications was more present in patients treated with biologicals, and also, the rate of patients vaccinated against Streptococcus pneumoniae increased significantly depending on the underlying treatment. Nevertheless, there was a discrepancy between vaccination awareness and actual vaccination rates for all cohorts.

• Sustained Remission After Combination Therapy with Rituximab and Etanercept in Two Patients with Rheumatoid Arthritis After TNF Failure: Case Report.

  Authors: Martin Feuchtenberger, Christian Kneitz, Petra Roll, Stefan Kleinert, Hans-Peter Tony

  The open rheumatology journal. 02/2009; 3:9-13.

  OBJECTIVES: Approximately up to 40% of patients with rheumatoid arthritis (RA) fail to respond to tumor necrosis factor (TNF) inhibitors, lose response over time or are unable to tolerate treatment.OBJECTIVES: Approximately up to 40% of patients with rheumatoid arthritis (RA) fail to respond to tumor necrosis factor (TNF) inhibitors, lose response over time or are unable to tolerate treatment. MATERIALS AND METHODOLOGY: We report two female patients suffering from active, refractory rheumatoid arthritis despite TNF blocking agents who have been treated with rituximab added to ongoing therapy with etanercept. RESULTS: Combination therapy was tolerated without any acute side effects. Both patients improved with a significant, long lasting reduction of disease activity (DAS28, CRP). Evaluation of the immunological parameters showed the expected B-cell depletion and a transient reduction of immunoglobulin-levels. One patient developed four serious infections requiring antibiotic treatment (1 pneumonia, 3 exacerbations of her pre-existing chronic bronchitis) within follow up of 45 months. CONCLUSION: Combination therapy of rituximab and etanercept lead to a significant improvement of clinical disease activity and inflammatory parameters in two RA patients refractory to anti-TNF treatment.

• Frequency of Regulatory T Cells is Not Affected by Transient B Cell Depletion Using Anti-CD20 Antibodies in Rheumatoid Arthritis.

  Authors: Martin Feuchtenberger, Sabine Müller, Petra Roll, Anne Waschbisch, Arne Schäfer, Christian Kneitz, Heinz Wiendl, Hans-Peter Tony

  The open rheumatology journal. 01/2008; 2:81-8.

  OBJECTIVES: Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristicOBJECTIVES: Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristic regeneration pattern of B cell subpopulations has been reported. However, little is known about the impact of B-cell depletion on peripheral T cells in particular regulatory T cells. MATERIALS AND METHODOLOGY: 17 patients with RA having failed anti-TNF were treated with rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16, CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up to 12 months after rituximab. In addition, quantification of the soluble form of the HLA class I molecule HLA-G by ELISA has been performed. RESULTS: Peripheral B cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+ lymphocytes showed no significant changes up to 1 year after B-cell depletion compared to before therapy. Only the relative frequency for CD3 and CD4 showed a significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive regulatory T cells remained constant. The percentage of HLA-G positive cells in the CD4+ or CD8+ population did not change significantly either. The amount of sHLA-G remained without significant changes. CONCLUSION: Absolute T cell counts showed no significant changes after rituximab compared to the time point before therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++ phenotype as well as positive Foxp3 expression were numerically stable. Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G showed no significant changes.

• Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development.

  Authors: Philipp Ströbel, Mirella Marino, Martin Feuchtenberger, Anne-Sophie Rouzière, Hans-Peter Tony, Ulrich Wulbrand, Reinhold Förster, Andreas Zettl, Nancy Lee Harris, Hans Kreipe, R Hubert Laeng, Hans Konrad Müller-Hermelink, Alexander Marx

  The Journal of pathology. 10/2005; 207(1):72-82.

  The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not aThe aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B-cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a 'high-risk' spectrum of chemokines due to local or genetic factors may interfere with B-cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed.

• Semiquantitative and qualitative assessment of B-lymphocyte V H repertoire by a fluorescent multiplex PCR.

  Authors: Martin Feuchtenberger, Hans-Peter Tony, Anne-Sophie Rouzière, Anette Jacobi, Thomas Dörner, Christian Kneitz, Petr Starostik

  Journal of immunological methods. 06/2003; 276(1-2):121-7.

  We established a new tool to perform semiquantitative and qualitative screening for V(H) gene usage frequency during IgH rearrangements in human B-lymphocytes. In two separate multiplex PCRs, theWe established a new tool to perform semiquantitative and qualitative screening for V(H) gene usage frequency during IgH rearrangements in human B-lymphocytes. In two separate multiplex PCRs, the rearranged VDJ regions were amplified with V(H) family-specific primers labeled with different fluorescent dyes (FAM, HEX, NED, or ROX). The relative amount of each of the particular V(H) family products and their ratios were determined by fragment analysis on a ABI PRISM 377 sequencer. We verified that the fluorescent multiplex PCR (FMPCR) shows high specificity and sensitivity, acceptable reproducibility and reliability. Data obtained were well in agreement with results revealed by sequencing following single-cell PCR. Ten healthy volunteers showed a comparable semiquantitative V(H) family distribution. The FMPCR also correctly detected a monoclonal peak in a CLL patient. Thus, labeling primers with various fluorescent dyes allows for an assessment of V(H) family usage and an immediate determination of the involved V(H) gene family if any clonal peaks are present. This method provides a quick, easy, and reliable tool for V(H) repertoire screening of larger populations of patients suffering from diseases with changes in the V(H) repertoire allowing for selection of cases worth a more detailed and cumbersome sequence analysis later on.

• Semiquantitative and qualitative assessment of B-lymphocyte VH repertoire by a fluorescent multiplex PCR

  Authors: Martin Feuchtenberger, Hans-Peter Tony, Anne-Sophie Rouzière, Anette Jacobi, Thomas Dörner, Christian Kneitz, Petr Starostik

  Journal of Immunological Methods.

  We established a new tool to perform semiquantitative and qualitative screening for VH gene usage frequency during IgH rearrangements in human B-lymphocytes. In two separate multiplex PCRs, theWe established a new tool to perform semiquantitative and qualitative screening for VH gene usage frequency during IgH rearrangements in human B-lymphocytes. In two separate multiplex PCRs, the rearranged VDJ regions were amplified with VH family-specific primers labeled with different fluorescent dyes (FAM, HEX, NED, or ROX). The relative amount of each of the particular VH family products and their ratios were determined by fragment analysis on a ABI PRISM 377 sequencer. We verified that the fluorescent multiplex PCR (FMPCR) shows high specificity and sensitivity, acceptable reproducibility and reliability. Data obtained were well in agreement with results revealed by sequencing following single-cell PCR. Ten healthy volunteers showed a comparable semiquantitative VH family distribution. The FMPCR also correctly detected a monoclonal peak in a CLL patient. Thus, labeling primers with various fluorescent dyes allows for an assessment of VH family usage and an immediate determination of the involved VH gene family if any clonal peaks are present. This method provides a quick, easy, and reliable tool for VH repertoire screening of larger populations of patients suffering from diseases with changes in the VH repertoire allowing for selection of cases worth a more detailed and cumbersome sequence analysis later on.

• Psoriatic arthritis: clinical spectrum and diagnostic procedures.

  Authors: Stefan Kleinert, Martin Feuchtenberger, Christian Kneitz, Hans-Peter Tony

  Clinics in dermatology. 25(6):519-23.

  Psoriatic arthritis presents with a broad clinical spectrum of symptoms. Symmetrical polyarthritis with joint pain and joint swelling is one pattern of clinical manifestations that often indicatesPsoriatic arthritis presents with a broad clinical spectrum of symptoms. Symmetrical polyarthritis with joint pain and joint swelling is one pattern of clinical manifestations that often indicates erosive progressive disease. Unlike in rheumatoid arthritis, the distal interphalangeal joints are regularly involved. Sometimes, the disease focuses on the larger joints of the lower extremities; iliosacral and intervertebral joints and tendons can also be involved. Thus, inflammatory back pain as well as any other prolonged joint pain in a patient with psoriasis is suspicious of psoriatic arthritis. This article reviews the clinical spectrum and diagnostic procedures that can lead to the diagnosis of psoriatic arthritis.

• Psoriatic arthritis: therapeutic principles.

  Authors: Martin Feuchtenberger, Stefan Kleinert, Hans-Peter Tony, Christian Kneitz

  Clinics in dermatology. 26(5):460-3.

  From the dermatologic point of view, psoriatic arthritis (PsA) was seen for a long time as a rare complication of psoriasis. Recent studies, however, reveal a high prevalence of PsA among patientsFrom the dermatologic point of view, psoriatic arthritis (PsA) was seen for a long time as a rare complication of psoriasis. Recent studies, however, reveal a high prevalence of PsA among patients with psoriasis, and the impact of PsA due to chronic inflammation of peripheral joints, axial joints, and periarticular structures leading to radiologic progression, functional impairment, and reduction in quality of life is well recognized. Substantial improvement in understanding immunopathology of PsA has led to a variety of new therapeutic options. This article reviews the current therapeutic principles for PsA.